Nationwide, approximately 30% of people with AIDS are injection drug abusers. Current data indicates that over half of new AIDS cases in New York city and many other Northeast urban areas occur in this population. Injection drug users themselves are not only at great risk for HIV disease, but also represent the major vector for heterosexual and perinatal transmission of HIV. The treatment of choice for opioid-dependent injection drug users with HIV disease is maintenance treatment with opioids. This group of patients has been seriously under represented in clinical trials of new therapies for HIV disease. As a result, there is little information available to guide the clinician in the treatment of these patients with antiretroviral agents. In addition, the reported effects of many of the newer HIV therapeutics on CYP45O enzyme function have generated concern that drug interactions between opioids and antiretrovirals will result in serious toxicity placing patients at risk for adverse events which could result in significant morbidity or noncompliance with treatment regimens. These concerns and the risk of developing drug resistant HIV often results in new HIV medications being denied to opioid-dependent patients, greatly reducing the treatment options and hastening the disease course. In this application, we propose a pilot study of once daily directly observed HAART therapy in methadone maintained patients. Pharmacokinetic studies will be undertaken prior to and following stabilization on the antiretroviral regimen to determine whether the antiretroviral therapeutics alter methadone metabolism. Antiretroviral concentrations will also be determined in a pharmacokinetic study and compared to historical controls to determine whether the disposition of these drugs are altered. Severity of addiction and psychiatric comorbidity will be assessed and correlated with treatment outcome defined by CD4 count, viral load, and illicit drug abuse over the course of a 6 month study period. This study will represent one of the first studies to determine whether once daily DOT in opioid replacement programs that also provide HIV care to patients is an effective modality for treating substance abusing patients with HIV disease. In addition, this study will show whether patients treated with methadone in 5-6 clinic visits weekly obtain benefit from these interventions. Should this treatment modality prove to be effective, it would provide a mechanism for allowing opioid dependent patients with HIV infection access to current therapies in a simplified medication regimen which would increase medication compliance, decrease viral spread, and slow the morbidity and mortality of HIV disease in this population.